In vitro evaluation of verapamil and other modulating agents in Brazilian chloroquine-resistant Plasmodium falciparum isolates

Menezes, Carla M. S.; Kirchgatter, Karin; Santi, Sílvia Maria Di; Savalli, Carine; Monteiro, Fabíola G.; Paula, Gilberto A.; Ferreira, Elizabeth Igne

doi:10.1590/s0037-86822003000100002

Cited by 10 publications

(9 citation statements)

References 20 publications

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“…(Table 3) Classical chemosensitizers, such as calcium channel blockers like verapamil, diltiazem, tiapamil (Fig. 4) or β-blockers like propanolol, are known to effectively overcome the CQ resistance in vitro [39,[132][133][134]. Verapamil reverses the CQ resistance of laboratory strains and in clinical isolates as well [133,135,136].…”

Section: Transporter Inhibitors and Modulators Of The Drug Resistancementioning

confidence: 99%

“…4) or β-blockers like propanolol, are known to effectively overcome the CQ resistance in vitro [39,[132][133][134]. Verapamil reverses the CQ resistance of laboratory strains and in clinical isolates as well [133,135,136]. Differentials in CQ uptake vs efflux in CQ-susceptible and resistant parasites have both been proposed as an explanation for the lower accumulation of CQ by the resistant parasites, but discussion has not ended yet [137][138][139][140].…”

Section: Transporter Inhibitors and Modulators Of The Drug Resistancementioning

confidence: 99%

“…5) can enhance in vitro the potency of CQ against P. falciparum CQ-resistant strains [132][133][134][156][157][158]. Phenothiazines have also been shown to reduce or reverse antibiotic resistance in bacteria [159][160][161] and in yeast [162].…”

Section: Phenothiazines (Antipsychotic Drugs) (Table 4)mentioning

confidence: 99%

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Chloroquine Resistance Reversal Agents as Promising Antimalarial Drugs

Henry¹,

Alibert²,

Orlandi-Pradines³

et al. 2006

CDT

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The development and spread of resistance to antimalarial drugs poses a severe and increasing public health threat. Failures of prophylaxis or treatment with quinolines, hydroxynaphthoquinones, sesquiterpene lactones, antifolate drugs and sulfamides are involved in a return malaria-related morbidity and mortality. Resistance is associated with a decrease in accumulation of drugs into the vacuole, which results from a reduced uptake of the drug, an increased efflux or a combination of both. A number of candidate genes in P. falciparum have been proposed to be involved in antimalarial resistance, each concerned in membrane transport. Weaker or stronger associations are seen in P. falciparum between the resistance to quinolines or artemisinin derivatives and codon changes in Pfmdr1, a gene which encodes Pgh-1, an ortholog of one of the P-glycoproteins expressed in multi-drug resistant human cancer cells (ABC transporter). Further analysis has revealed a new gene, Pfcrt, encoding a PfCRT protein, which resembles an anion channel. Codon changes found in the Pfcrt sequence in drug resistant isolates could facilitate the drug efflux through a putative channel. It has been proposed that the reversal of quinoline resistance by verapamil is due to hydrophobic binding to the mutated PfCRT protein. Several compounds have demonstrated in the past decade a promising capability to reverse the antimalarial drug resistance in vitro in parasite isolates, in animal models and in human malaria. These drugs belong to different pharmacological classes such as calcium channel blockers, tricyclic antidepressants, antipsychotic calmodulin antagonists, histamine H1-receptor antagonists, analgesic and antipyretic drugs, non-steroidal anti-inflammatory drugs, and to different chemical classes such as synthetic surfactants, alkaloids from plants used in traditional medicine, pyrrolidinoaminoalkanes and anthracenic derivatives. Here we summarize the progress made in biochemical and genetic basis of antimalarial resistance, emphasizing the recent developments on drugs, which interfere with trans membrane proteins involved in drug efflux or uptake.

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Section: Transporter Inhibitors and Modulators Of The Drug Resistancementioning

confidence: 99%

Section: Transporter Inhibitors and Modulators Of The Drug Resistancementioning

confidence: 99%

See 1 more Smart Citation

Chloroquine Resistance Reversal Agents as Promising Antimalarial Drugs

Henry¹,

Alibert²,

Orlandi-Pradines³

et al. 2006

CDT

View full text Add to dashboard Cite

show abstract

“…Classical chemosensitizers, such as calcium channel blockers like verapamil, diltiazem, tiapamil or β-blockers like propanolol, are known to efficiently overcome the CQ resistance in vitro [33,147,[249][250][251]. Verapamil reverses the CQ resistance of laboratory strains and clinical isolates as well [250,252,253].…”

Section: -Transporter Inhibitors and Modulators Of The Multidrug Resimentioning

confidence: 99%

“…Verapamil reverses the CQ resistance of laboratory strains and clinical isolates as well [250,252,253]. Differentials in drug uptake vs efflux in CQ-susceptible and -resistant parasites have both been proposed as an explanation for the lower CQ accumulation by the resistant parasites, but the discussion is not ended [254][255][256][257].…”

Section: -Transporter Inhibitors and Modulators Of The Multidrug Resimentioning

confidence: 99%

Chemosensitizers in Drug Transport Mechanisms Involved in Protozoan Resistance

Pradines

Pages²,

Barbe³

2005

CDTID

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The emergence and spread of antiparasitic drug resistance pose a severe and increasing public health threat. Failures in prophylaxis or those in treatment with quinolines, hydroxynaphtoquinones, sesquiterpenic lactones, antifolate drugs, arsenic and antimony containing drugs sulfamides induce reemergence of parasitic-related morbidity and mortality. Resistance is often associated with alteration of drug accumulation into parasites, which results from a reduced uptake of the drug, an increased efflux or, a combination of the two processes. Resistance to quinolines, artemisinin derivatives and arsenicals and expression of an active efflux mechanism are more or less correlated in protozoa like Plasmodium spp., Leishmania spp., and Trypanosoma spp. Various parasite candidate genes have been proposed to be involved in drug resistance, each concerned in membrane transport. Genes encoding membrane glycoproteins, orthologue to the P-glycoproteins identified in MDR human cancer cells, have been described in these resistant pathogens in addition to various membrane proteins involved in drug transport. Several compounds have demonstrated, in the past decade, promising capability to reverse the drug resistance in parasite isolates in vitro, in animal models and for human malaria. These drugs belong to different pharmacological classes such as calcium channel blockers, tricyclic antidepressants, antipsychotic calmodulin antagonists, histamine H1-receptor antagonists, analgesic antipyretic drugs, non-steroidal anti-inflammatory drugs, and to different chemical classes such as synthetic surfactants, alkaloids from plants used in traditional medicine, pyrrolidinoaminoalkanes and derivatives, and anthracene derivatives. Here, are summarized the molecular bases of antiparasitic resistance emphasizing recent developments with compounds acting on trans-membrane proteins involved in drug efflux or uptake.

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ABC Proteins Involved in Protozoan Parasite Resistance

Pradines

2009

ABC Transporters and Multidrug Resistance

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In vitro evaluation of verapamil and other modulating agents in Brazilian chloroquine-resistant Plasmodium falciparum isolates

Cited by 10 publications

References 20 publications

Chloroquine Resistance Reversal Agents as Promising Antimalarial Drugs

Chloroquine Resistance Reversal Agents as Promising Antimalarial Drugs

Chemosensitizers in Drug Transport Mechanisms Involved in Protozoan Resistance

ABC Proteins Involved in Protozoan Parasite Resistance

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